Project Summary/Abstract Congenital heart defects characterized by severe hypoplasia of one of the ventricles (so-called single ventricles) are not compatible with life, particularly when there is severe obstruction to pulmonary or systemic blood flow. Thanks to a series of palliative procedures undertaken to convert the single ventricle into the ?systemic ventricle?, thousands of patients have survived beyond childhood. The last of such procedures, the Fontan operation, is characterized by diverting venous blood return from the upper and lower body directly into the pulmonary arteries in the absence of a subpulmonary ventricle. Although Fontan patients are now reaching early adulthood with a heart defect that was uniformly fatal, they experience substantial morbidity and early mortality, with progressive decline in exercise performance and functional capacity as well as early death related to heart failure and complications related to Fontan physiology. The relationship of contractile reserve, or the ability to augment ventricular function under stress, and exercise capacity is not well understood in these patients. Most studies examining the association between exercise capacity and ventricular function have used resting, load-dependent echocardiographic indices of function and have used pharmacologic stress rather than physical exercise. A newer technique speckle tracking echocardiography assesses cardiac mechanics through myocardial deformation, or strain. Strain is a sensitive, relatively load independent measure of contractility thought to be abnormal before overt changes in conventional measures of pump function, such as ejection fraction, are seen. Therefore, strain might be a more useful measure to assess ventricular function. The overall goal of this proposal is to examine the cardiac mechanics at rest and peak exercise in patients after the Fontan operation and its association with measures of exercise performance. To accomplish this objective, we propose a prospective pilot study of 60 subjects undergoing cardiopulmonary exercise testing that will undergo echocardiogram at rest and at peak exercise. In Aim 1 we will determine the changes from rest to peak exercise in ventricular function (called contractile reserve) using strain, and the transpulmonary gradient, measured as the mean Fontan fenestration gradient when one is present. In Aim 2, we will establish the association of contractile reserve with measures of exercise performance in the same patient population. This study will provide insight into the ventricular contractility/response to exercise in patients after Fontan operation. While the determinants of exercise performance in Fontan patients are multifactorial, we believe this study will inform whether diminished contractility at rest or impaired contractile reserve are associated with abnormal measures of exercise capacity independently of other factors. These results could potentially inform therapeutic strategies in this population. Completion of this study will allow Dr. Bhatt to develop her skills by conducting patient-oriented research using non-invasive imaging tools in a mentored fashion and will provide preliminary data for a (K23) Career Development Award, fostering her development towards independence.